FIG. 8.

Proposed interactions between Grx1 and cytosolic enzymes. (A) Reduced Grx1 is shown bound to ASK1 in MCF-7/ADR (multidrug-resistant breast cancer) cells under resting conditions (120). On glucose deprivation, the GSH/GSSG ratio decreases, resulting in oxidation of thiols in the Grx1 active site and disruption of its association with ASK1. Dissociation of Grx1 and ASK1 leads to ASK1 activation and increased apoptosis. (B) Grx1 and caspase-3 are shown associated under nonstressed conditions in BAECs. TNF-α–induced activation of Grx leads to pro-caspase-3 deglutathionylation, release from the complex, and cleavage by caspase-8 to active caspase-3, triggering apoptosis (94).